Predicting lymphatic filariasis elimination in data-limited settings: A reconstructive computational framework for combining data generation and model discovery.

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps.

Two Nigerian States (Plateau and Nasarawa) Have Eliminated Transmission of Human Onchocerciasis-A Report of Post-Ivermectin Mass Drug Administration Surveillance.

Transmission of Onchocerca volvulus (causing "river blindness") was interrupted in two states of Nigeria (Plateau and Nasarawa) in 2017 in accordance with 2016 WHO guidelines. Ivermectin mass drug administration was halted in January 2018, and posttreatment surveillance activities were conducted over a 3-year period. Vector Simulium damnosum s.l. flies were collected during the 2019 (39 sites) and 2020 (42 sites) transmission seasons. Head pools were tested by polymerase chain reaction for the presence of third-stage O. volvulus larvae; 15,585 flies were all negative, demonstrating an infective rate of < 1/2,000 with 95% confidence. In 2021, the Nigerian Federal Ministry of Health declared the two-state area as having eliminated transmission. Plateau and Nasarawa states are the first of 30 endemic states in Nigeria to have met the WHO criteria for onchocerciasis elimination. Post-elimination surveillance will need to continue given the risk of reintroduction of transmission from neighboring states.

Impact of Three to Five Rounds of Mass Drug Administration on Schistosomiasis and Soil-Transmitted Helminths in School-Aged Children in North-Central Nigeria.

Nasarawa and Plateau states of north-central Nigeria have implemented programs to control schistosomiasis (SCH) and soil-transmitted helminths (STH) in children since the 1990s. Statewide mapping surveys were conducted in 2013, when 11,332 school-aged children were sampled from 226 schools. The local government areas (LGAs) then received varying combinations of mass drug administration (MDA) for the next 5 years. We revisited 196 (87%) schools in 2018 plus an additional six (202 schools in total), sampling 9,660 children. We calculated overall prevalence and intensity of infection and evaluated associations with gender; age; behaviors; water, sanitation, and hygiene (WASH); and treatment regimen. Urine heme detection dipsticks were used for Schistosoma hematobium in both surveys, with egg counts added in 2018. Stool samples were examined by Kato-Katz for Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni, and hookworm. Schistosomiasis prevalence among sampled students dropped from 12.9% (95% confidence interval [CI]: 11.1-14.9%) to 9.0% (95% CI: 7.5-10.9%), a statistically significant change (P < 0.05). In 2018, eight LGAs still had > 1% of children with heavy-intensity schistosome infections. Prevalence of STH infection did not significantly change, with 10.8% (95% CI: 9.36-12.5%) of children positive in 2013 and 9.4% (95% CI: 8.0-10.9%) in 2018 (P = 0.182). Heavy-intensity STH infections were found in < 1% of children with hookworm, and none in children with A. lumbricoides or T. trichiura in either study. The WASH data were collected in 2018, indicating 43.6% of schools had a latrine and 14.4% had handwashing facilities. Although progress is evident, SCH remains a public health problem in Nasarawa and Plateau states.

Post-Treatment Surveillance for Lymphatic Filariasis in Plateau and Nasarawa States, Nigeria: Results of Transmission Assessment Surveys.

Following the halt of mass drug administration (MDA) for lymphatic filariasis (LF), the WHO recommends at least 4 years of post-treatment surveillance (PTS) to confirm that transmission recrudescence or importation does not occur. The primary means of evaluation during PTS is repeated transmission assessment surveys (TASs) conducted at 2- to 3-year intervals after TAS-1 stop-MDA surveys. This study reports the results of TAS-2 and TAS-3 surveys in Plateau and Nasarawa states (pop. 6.9 million) of Nigeria divided into a minimum of seven evaluation units (EUs) per TAS. A total of 26,536 first- and second-year primary school children (approximately 6-7 years old) were tested for circulating filarial antigen (CFA) between 2014 and 2017. Of 12,313 children tested in TAS-2 surveys, only five (0.04%) were CFA positive, with no more than two positive samples from any one EU, which was below the critical value of 20 per EU. Of 14,240 children tested in TAS-3 surveys, none (0%) were CFA positive. These results indicate that LF transmission remains below sustainable transmission levels and suggest that elimination of transmission has been achieved in Plateau and Nasarawa, Nigeria.

The Interruption of Transmission of Human Onchocerciasis by an Annual Mass Drug Administration Program in Plateau and Nasarawa States, Nigeria.

Plateau and Nasarawa states in central Nigeria were endemic for onchocerciasis. The rural populations of these two states received annual ivermectin mass drug administration (MDA) for a period of 8-26 years (1992-2017). Ivermectin combined with albendazole was given for 8-13 of these years for lymphatic filariasis (LF); the LF MDA program successfully concluded in 2012, but ivermectin MDA continued in areas known to have a baseline meso-/hyperendemic onchocerciasis. In 2017, serological and entomological assessments were undertaken to determine if MDA for onchocerciasis could be stopped in accordance with the current WHO guidelines. Surveys were conducted in 39 sites that included testing 5- to < 10-year-old resident children by using ELISA for OV16 IgG4 antibodies, and Onchocerca volvulus O150 pooled polymerase chain reaction (PCR) testing of Simulium damnosum s.l. vector heads. Only two of 6,262 children were OV16 positive, and none of 19,056 vector heads were positive for parasite DNA. Therefore, both states were able to meet WHO stop-MDA thresholds of an infection rate in children of < 0.1% and a rate of infective blackflies of <1/2,000, with 95% statistical confidence. Transmission of onchocerciasis was declared interrupted in Plateau and Nasarawa states by the Federal Ministry of Health, and 2.2 million ivermectin treatments/year were stopped in 2018. Post-treatment Surveillance was launched focusing on entomological monitoring on borders with neighboring onchocerciasis-endemic states. An apparent positive impact of the LF MDA program on eliminating hypo-endemic onchocerciasis was observed. This is the first stop-MDA decision for onchocerciasis in Nigeria and the largest single stop-MDA decision for onchocerciasis yet reported. This achievement, along with the process used in adapting and implementing the 2016 WHO stop-MDA guidelines, will be important as a potential model for decision makers and national onchocerciasis elimination committees in other African countries that are charged with advancing their programs.